HAMLET (human alpha-lactalbumin made lethal to tumor cells) triggers autophagic tumor cell death

HAMLET, a complex of partially unfolded alpha-lactalbumin and oleic acid, kills a wide range of tumor cells. Here we propose that HAMLET causes macroautophagy in tumor cells and that this contributes to their death. Cell death was accompanied by mitochondrial damage and a reduction in the level of active mTOR and HAMLET triggered extensive cytoplasmic vacuolization and the formation of double-membrane-enclosed vesicles typical of macroautophagy. In addition, HAMLET caused a change from uniform (LC3-I) to granular (LC3-II) staining in LC3-GFP-transfected cells reflecting LC3 translocation during macroautophagy, and this was blocked by the macroautophagy inhibitor 3-methyladenine. HAMLET also caused accumulation of LC3-II detected by Western blot when lysosomal degradation was inhibited suggesting that HAMLET caused an increase in autophagic flux. To determine if macroautophagy contributed to cell death, we used RNA interference against Beclin-1 and Atg5. Suppression of Beclin-1 and Atg5 improved the survival of HAMLET-treated tumor cells and inhibited the increase in granular LC3-GFP staining. The results show that HAMLET triggers macroautophagy in tumor cells and suggest that macroautophagy contributes to HAMLET-induced tumor cell death.

Hamlet's Mobility: The Reception of Shakespeare's Tragedy in US-American and Canadian Narrative Fiction

This essay presents a comprehensive study of how Hamlet figures in North American fiction. Gabriele Rippl takes her cue from Stephen Greenblatt’s notion of Shakespeare’s ‘theatrical mobility’ (Greenblatt, Cultural Mobility. Cambridge University Press, 2010). This initial mobility, based on the playwright’s own borrowings, appears to facilitate, or even instigate further migrations. Rippl proceeds to give an overview of adaptations of Shakespeare’s Hamlet in the USA and Canada, thus providing an insight into the historical and cultural uses to which the play has been put by authors such as John Updike or Margaret Atwood. Phenomena such as the ‘republicanization’ of Shakespeare (James Fenimore Cooper), or his appropriation for a feminist counter-discourse in Canada circumscribe a space for the negotiation of cultural and political identities.